This study will contribute to the understanding of sexual differentiation (SD) and monoamine (MA) function, both of which have important clinical significance. Malfunction of SD results in serious neuroendocrine disorders in the adult. The roles that MA's play in SD are clinically important in relation to the widespread use of MA-modifying drugs in psychiatry, neurology, and mood control. The health-related consequences of exposing the fetus or neonate to these drugs through maternal use are not presently understood but are to be investigated by this project. Basically, sexual differentiation of the gonadotropic hormone (GTH) secretion pattern is due to the action of neonatal testicular androgen on the hypothalamus in permanently suppressing the cyclic, female pattern and inducing the tonic pattern of the male. Hypothalamic monoamines (MA's) have been found to play essential roles in GTH regulation, but little is known about the function of MA's in SD of GTH secretion pattern. Male pups will be treated during the neonatal critical period for SD with MA-modifying agents. Subsequently, they will be castrated and implanted with subcutaneous grafts of ovarian and vaginal tissue. The rats will be terminated as adults and the transplanted tissue examined histologically. Whether early exposure to MA-modifying agents has affected the SD of the GTH secretion pattern can be reliably inferred from the morphology of the ovarian and vaginal transplants. Sham-treated controls will match each treatment group. Initially, pups will be treated with MA antagonists administered systemically. Those antagonists that did modify SD will next be administered along with repletion agents that should restore the MA's and result in normal SD. Having confirmed the identify of the MA's active in SD, their antagonists will be implanted in various loci of the hypothalamus. When the loci at which hypothalamic MA's are active in SD have been thus identified, these sites will be verified by combining hypothalamic implants of antagonists with systemic administration of repletion agents. Thus, not only will knowledge about roles of MA's in SD be advanced, the hypothalamic structures involved will be indicated.